Synthesis and in vitro activity of asymmetric indole-based bisamidine compounds against Gram-positive and Gram-negative pathogens

Bioorg Med Chem Lett. 2020 Apr 15;30(8):126887. doi: 10.1016/j.bmcl.2019.126887. Epub 2019 Dec 13.

Abstract

A series of new asymmetric bisamidine was designed, synthesized, and tested for their in-vitro antibacterial activity using a range of Gram-positive and Gram-negative pathogens. Most compounds demonstrated powerful antibacterial activity, and interestingly, some displayed better activity against several Gram-negative strains than the lead compound 1. The most potent bisamidine 8l exhibited 4-fold more potent activity against E. coli, K. pneumonia, P. aeruginosa, and C. freundii than compound 1. Especially 8l exhibited a powerful activity against K. pneumonia secreting NDM-1 enzyme with a minimum inhibitory concentration (MIC) of 2 μg/mL, while levofloxacin and vancomycin displayed resistance, with MICs > 128 μg/mL.

Keywords: Antibacterial activity; Bisamidine; Gram-negative pathogens; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Citrobacter freundii / drug effects
  • Dose-Response Relationship, Drug
  • Escherichia coli / drug effects
  • Furans / chemical synthesis
  • Furans / chemistry
  • Furans / pharmacology*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Klebsiella / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pseudomonas aeruginosa / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Furans
  • Indoles
  • bisamidine
  • indole